Zinc in PDB 4wcu: PDE4 Complexed with Inhibitor

All present enzymatic activity of PDE4 Complexed with Inhibitor:
3.1.4.53;

The structure of PDE4 Complexed with Inhibitor, PDB code: 4wcu was solved by M.D.Sorensen, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	92.85 / 2.35
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	99.232, 113.545, 160.535, 90.00, 90.00, 90.00
R / Rfree (%)	24.4 / 30.4

The structure of PDE4 Complexed with Inhibitor also contains other interesting chemical elements:

Magnesium	(Mg)	4 atoms
Chlorine	(Cl)	8 atoms

The binding sites of Zinc atom in the PDE4 Complexed with Inhibitor (pdb code 4wcu). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 4 binding sites of Zinc where determined in the PDE4 Complexed with Inhibitor, PDB code: 4wcu:
Jump to Zinc binding site number: 1; 2; 3; 4;

Zinc binding site 1 out of 4 in the PDE4 Complexed with Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of PDE4 Complexed with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn501 b:45.9 occ:1.00 NE2 A:HIS200 2.2 27.4 1.0 NE2 A:HIS164 2.2 37.9 1.0 OD2 A:ASP201 2.3 26.2 1.0 OD1 A:ASP318 2.3 32.9 1.0 CD2 A:HIS200 3.0 26.4 1.0 CE1 A:HIS164 3.1 37.8 1.0 CG A:ASP318 3.2 33.3 1.0 CG A:ASP201 3.2 25.8 1.0 CE1 A:HIS200 3.3 27.2 1.0 CD2 A:HIS164 3.3 36.9 1.0 OD2 A:ASP318 3.3 31.4 1.0 OD1 A:ASP201 3.5 24.2 1.0 MG A:MG502 4.0 20.6 1.0 CG A:HIS200 4.1 27.1 1.0 CD2 A:HIS160 4.2 34.1 1.0 ND1 A:HIS164 4.3 38.3 1.0 ND1 A:HIS200 4.3 25.6 1.0 NE2 A:HIS160 4.3 34.1 1.0 CG A:HIS164 4.4 36.9 1.0 CB A:ASP201 4.5 26.0 1.0 CB A:ASP318 4.5 34.6 1.0 CG2 A:VAL168 4.7 32.5 1.0 CL8 A:3KQ500 5.0 46.4 1.0

Zinc binding site 2 out of 4 in the PDE4 Complexed with Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of PDE4 Complexed with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn501 b:44.0 occ:1.00 NE2 B:HIS164 2.2 31.6 1.0 OD2 B:ASP201 2.3 32.0 1.0 OD1 B:ASP318 2.3 35.7 1.0 NE2 B:HIS200 2.5 33.2 1.0 CE1 B:HIS164 3.2 31.6 1.0 CG B:ASP318 3.2 36.2 1.0 CG B:ASP201 3.2 30.6 1.0 CD2 B:HIS164 3.3 31.9 1.0 CD2 B:HIS200 3.3 32.5 1.0 OD2 B:ASP318 3.4 35.7 1.0 CE1 B:HIS200 3.6 33.1 1.0 OD1 B:ASP201 3.6 30.2 1.0 CD2 B:HIS160 3.9 34.9 1.0 MG B:MG502 4.0 29.6 1.0 NE2 B:HIS160 4.1 35.1 1.0 O B:HOH638 4.3 29.2 1.0 ND1 B:HIS164 4.3 31.6 1.0 CG B:HIS164 4.4 33.1 1.0 CB B:ASP201 4.4 30.8 1.0 CG B:HIS200 4.5 31.4 1.0 CB B:ASP318 4.6 36.9 1.0 ND1 B:HIS200 4.6 31.6 1.0 CG2 B:VAL168 4.7 34.6 1.0 CL8 B:3KQ500 4.9 45.1 1.0 CE2 B:TYR159 5.0 36.1 1.0

Zinc binding site 3 out of 4 in the PDE4 Complexed with Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of PDE4 Complexed with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn501 b:48.1 occ:1.00 NE2 C:HIS164 2.2 36.6 1.0 OD1 C:ASP318 2.3 34.5 1.0 OD2 C:ASP201 2.3 31.2 1.0 NE2 C:HIS200 2.5 29.4 1.0 CE1 C:HIS164 3.1 37.1 1.0 CG C:ASP318 3.1 36.6 1.0 CD2 C:HIS164 3.3 37.3 1.0 CG C:ASP201 3.3 29.5 1.0 OD2 C:ASP318 3.3 35.0 1.0 CD2 C:HIS200 3.4 28.7 1.0 CE1 C:HIS200 3.5 28.0 1.0 OD1 C:ASP201 3.8 30.8 1.0 MG C:MG502 3.9 26.9 1.0 CD2 C:HIS160 3.9 34.5 1.0 ND1 C:HIS164 4.3 37.3 1.0 NE2 C:HIS160 4.3 34.4 1.0 O C:HOH634 4.3 28.8 1.0 CG C:HIS164 4.4 37.1 1.0 CG C:HIS200 4.5 28.3 1.0 ND1 C:HIS200 4.5 28.4 1.0 CB C:ASP201 4.5 29.1 1.0 CB C:ASP318 4.6 36.9 1.0 CL8 C:3KQ500 4.7 45.9 1.0 CG2 C:VAL168 4.8 38.8 1.0

Zinc binding site 4 out of 4 in the PDE4 Complexed with Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 4 of PDE4 Complexed with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ D:Zn501 b:50.7 occ:1.00 NE2 D:HIS164 2.2 39.2 1.0 OD1 D:ASP318 2.3 40.5 1.0 NE2 D:HIS200 2.4 36.4 1.0 OD2 D:ASP201 2.5 38.4 1.0 CD2 D:HIS200 3.0 36.6 1.0 CE1 D:HIS164 3.1 38.9 1.0 CD2 D:HIS164 3.2 39.2 1.0 CG D:ASP318 3.2 41.7 1.0 CG D:ASP201 3.3 37.7 1.0 OD2 D:ASP318 3.5 42.0 1.0 CE1 D:HIS200 3.5 36.3 1.0 OD1 D:ASP201 3.6 37.0 1.0 MG D:MG502 3.9 30.9 1.0 CD2 D:HIS160 4.0 39.3 1.0 ND1 D:HIS164 4.2 39.0 1.0 NE2 D:HIS160 4.3 39.1 1.0 CG D:HIS164 4.3 39.4 1.0 CG D:HIS200 4.3 36.4 1.0 ND1 D:HIS200 4.5 36.2 1.0 CB D:ASP201 4.5 37.1 1.0 CB D:ASP318 4.6 42.0 1.0 CG2 D:VAL168 4.7 42.0 1.0 CL8 D:3KQ500 4.9 52.4 1.0 CA D:ASP318 5.0 42.4 1.0

J.Felding, M.D.Sorensen, T.D.Poulsen, J.Larsen, C.Andersson, P.Refer, K.Engell, L.G.Ladefoged, T.Thormann, A.M.Vinggaard, P.Hegardt, A.Sohoel, S.F.Nielsen. Discovery and Early Clinical Development of 2-{6-[2-(3,5-Dichloro-4-Pyridyl)Acetyl]-2, 3-Dimethoxyphenoxy}-N-Propylacetamide (Leo 29102), A Soft-Drug Inhibitor of Phosphodiesterase 4 For Topical Treatment of Atopic Dermatitis. J. Med. Chem. V. 57 5893 2014.
ISSN: ISSN 0022-2623
PubMed: 24984230
DOI: 10.1021/JM500378A